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SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.

Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

We report 2 unusual autopsy cases with head handgun wounds using defective firearms in a suicidal context. In the first case, a 78-year-old man was found hanged from a tree, with a Lefaucheux revolver lying on the tree. In the right temporal region, there was an entrance wound with a bullet still in place, responsible for a mild cerebral contusion, without bone defect. The main cause of death was hanging. In the second case, a 60-year-old man died at home after shooting himself in the head several times with a 22-long rifle revolver. The autopsy showed 13 entrance wounds on the scalp. Most of the bullets remained along the skull vault. In each of 2 cases, the manner of death, the feasibility of suicidal gesture, and the consequences of a brain injury on the time to the occurrence of incapacity were questioned. These unusual autopsy cases underline how important it is to take into account the defective nature of firearms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy., Graphical abstract, Cell biology; Molecular physiology; Virology

Exposure to metals and trace elements (TE) is universal and can cause toxicity in case of excessive exposure. We evaluated the concentrations and tissue distribution of 39 TE using high-resolution ICP-MS after total mineralization by microwave in twenty autopsied French subjects. We found a globally homogeneous distribution of TE in the body, with some accumulations in agents, involved in respiratory pathologies and classified as carcinogens, in the lungs. The liver, an organ of metabolism, appeared to concentrate Co, Fe, La, Mn, Mo, Pb and Zn. Fe seemed to accumulate in the spleen, the organ of hematopoiesis. The kidney showed high concentrations of some TE, which can cause nephrotoxicity. The use of microwave mineralization and high-resolution ICP-MS allowed accurate quantification and a very high sensitivity, without spectral interferences. The results obtained in this study could be used to support the interpretation of post-mortem metal concentrations in tissues.

Untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) techniques have become indispensable tools for systematic toxicological analysis. They allow the research of an almost unlimited number of drugs within a single analytical cycle, but shared mass spectra libraries are still missing to identify newly marketed compounds, along with defined analytical procedures. This article describes the optimization, validation, and application of an untargeted screening method devoted to hair analysis using data-dependent analysis (DDA) and a shared HRMS database. This method used an ultra-high performance liquid chromatography coupled to a benchtop Orbitrap. Raw MS data were processed with Compound Discoverer software coupled to the mzCloud™ library. Optimizations were performed on blank hair spiked with 19 analytes having different physical and chemical properties. To validate the effectiveness of a shared spectra database, 20 compounds spectra were added and then retrospectively screened. Sensitivity and reliability were evaluated on 317 compounds of interest in toxicology. The method was then applied to 11 hair samples. The matrix effect range by ion suppression/enhancement was 40%-110%. The method allows the detection of 284 among the 317 screened compounds, including 72 new psychoactive substances (NPS). Lower limit of identification (LLOI) and lower limit of detection (LLOD) were 1 to 1000 pg/mg and 1 to 500 pg/mg, respectively. The method was successfully applied to 11 clinical cases and 144 compounds were identified including 24 NPS including AKB48-5F for the first time in hair. We developed and validated an LC-HRMS untargeted screening of 284 compounds and successfully applied it to 11 real hair samples.

Resume Le cannabis est le stupefiant le plus consomme en France. Sa toxicite neuropsychiatrique est bien connue et la litterature recente semble evoquer une toxicite cardiaque. Entre 2001 et 2016, nous avons identifie 33 deces pour lesquels une origine cardiaque etait identifiee ou envisagee a l’autopsie et/ou a l’examen anatomopathologique et pour lesquels seul un cannabinoide a ete mis en evidence dans le sang au niveau de l’analyse toxicologique de recherche de causes de deces. L’etude de ces cas a montre qu’il s’agissait majoritairement de sujets masculins (90 %) avec un âge median de 37 ans [IQ25–75 = 29–44]. Du (−)−Δ9 tetrahydrocannabinol (THC) et du 11-nor-tetrahydrocannabinol carboxylique (THC-COOH) ont ete retrouves dans le sang pour l’ensemble des cas avec des concentrations medianes (intervalle interquartile IQ25–75) respectives de 2,9 ng/mL (IQ25–75 1,5–6,5) pour le THC et 28 ng/mL (IQ25–75 12–43) pour le THC-COOH. Le 11-hydroxy-tetrahydrocannabinol (11-OH-THC) a ete mis en evidence chez 21 personnes avec une concentration mediane de 1,55 ng/mL (IQ25–75 0,8–2,8), temoignant d’une derniere prise recente avant le deces. Parmi ces 33 personnes, 14 ont pu etre identifiees comme etant des consommateurs chroniques et 2 comme etant des consommateurs occasionnels de cannabis. Il n’existait pas de donnees pour les autres. Les causes de deces observees etaient majoritairement des maladies coronariennes (n = 20) mais il a egalement ete mis en evidence des cardiomyopathies (n = 8), des myocardites (n = 2) et des causes autres (n = 3). L’etude de l’evolution des cas semble en faveur d’une tendance a l’augmentation pouvant eventuellement etre mise en relation avec l’evolution des teneurs en cannabinoides des plantes et resines observee ces dernieres annees. Bien que le mecanisme d’action de cette cardiotoxicite ne soit pas encore elucide, plusieurs liens semblent exister entre le systeme endocannabinoide et le systeme cardiovasculaire. Le cannabis pourrait donc apparaitre comme un facteur de risque cardiovasculaire a prendre en compte et dont la consommation devrait etre recherchee notamment chez les sujets jeunes presentant des troubles cardiovasculaires.

Summary Adipocere formation requires very particular conditions of humidity and pH, but when it is formed, it can persist for very long periods. To date, there are very few cases with toxicological analyses performed on adipocere. We report two cases with a long delay between death and the discovery of the body (24 days and 12 years) associated with adipocere formation. In both cases a screening was carried out by GC-MS and LC-DAD. Additionally, a LC-MS/MS screening for drug facilitated sexual assault was performed allowing the detection of psychotropic substances at very low levels. Adipocere samples were hydrolyzed with a lipase buffer before liquid-liquid extraction. In the first case, diazepam, nordazepam and flunitrazepam were found at 2.1 ng/g, 1.8 ng/g and 1.2 ng/g, respectively. In case 2, phenobarbital was found at 26 μg/g in adipocere and 59 μg/g in liver. Although the post-mortem delay was important and the environmental conditions may have affected the measured concentrations, we were able to highlight the presence of 3 benzodiazepines and a barbiturate. The interpretation of these results remains complicated because of the lack of data in the literature.

Suicide is one of the most disastrous outcomes for psychiatric disorders. Recent advances in biological psychiatry have suggested a positive relationship between some specific brain abnormalities and specific symptoms in psychiatric disorders whose organic bases were previously completely unknown. Microglia, immune cells in the brain, are regarded to play crucial roles in brain inflammation by releasing inflammatory mediators and are suggested to contribute to various psychiatric disorders such as depression and schizophrenia. Recently, activated microglia have been suggested to be one of the possible contributing cells to suicide and suicidal behaviors via various mechanisms especially including the tryptophan-kynurenine pathway. Animal model research focusing on psychiatric disorders has a long history, however, there are only limited animal models that can properly express psychiatric symptoms. In particular, to our knowledge, animal models of human suicidal behaviors have not been established. Suicide is believed to be limited to humans, therefore human subjects should be the targets of research despite various ethical and technical limitations. From this perspective, we introduce human biological studies focusing on suicide and microglia. We first present neuropathological studies using the human postmortem brain of suicide victims. Second, we show recent findings based on positron emission tomography (PET) imaging and peripheral blood biomarker analysis on living subjects with suicidal ideation and/or suicide-related behaviors especially focusing on the tryptophan-kynurenine pathway. Finally, we propose future perspectives and tasks to clarify the role of microglia in suicide using multi-dimensional analytical methods focusing on human subjects with suicidal ideation, suicide-related behaviors and suicide victims.

A manner of death may be ruled undetermined by the forensic pathologist when there is insufficient information about the circumstances surrounding the death to make a ruling. The aim of our study was to retrospectively analyze a series of autopsy cases that were classified as undetermined manner of death after complete investigations. In all, 48 cases were examined. In 23 cases (48%), the cause of death was determined. The most frequent cause of death was toxic death (n = 11). More than one manner of death was deemed conceivable for most cases (n = 39). The most frequent and the most probable manner of death was accident (n = 37). Homicide was not excluded in about 23% of the cases. Our study showed that the manner of death may remain undetermined despite an established cause of death, and even when two or more conceivable causes of death are considered. Our study pointed out that undetermined manner of death covers a wide range of situations and that homicide may be underestimated.

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death. Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs. The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group. According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

Determination of the manner of death is a major issue in forensic practice. Differentiating the injuries caused by falls from a low height from injuries due to the deliberate application of a blunt object can be difficult. A few studies suggested the use of certain criteria, such as the hat brim line rule, to help in differentiating between falls and blows. Unfortunately they are not consistent. All autopsy cases from a 16-year period (1996–2012) were analyzed retrospectively. Three groups were defined: homicide cases (n = 31), sudden natural deaths involving a fall (n = 103), and accidental fall cases (n = 30). The three groups were statistically compared across a wide range of parameters including general characteristics, presence, and characteristics of different types of wounds (lacerations, deep bruises, fractures, intracranial trauma, and defense injuries) as well as their respective anatomical site. There were marked differences in wounds between homicide and fall cases, e.g., wounds were more numerous and larger in homicides. We did not confirm the hat brim line rule as a reliable discriminating parameter. A simple and highly effective multivariate model was found, which included the presence of lacerations, deep bruises, and intracranial trauma. This study underlines the importance of autopsy findings in providing an indication of the manner of death. Conversely, the limitations of the hat brim line rule have been highlighted.

We present the case of a reciprocal homicide by stabbing that occurred within an unmarried couple without known history of spousal violence. Each partner killed the other one at the same time and at the same place using kitchen knives. They were both found dead at home lying on the floor after the neighbors heard an argument and screams coming from the couple's apartment, so they called the police and the fire department. The door was locked from the inside, and the fire department was forced to break the door. Two kitchen knives supporting blood traces were found at the scene. At autopsy, both bodies showed multiple stab wounds, and the lethal ones were due to heart injuries. Defense injuries were also found in both bodies. To our knowledge, this is the first case of reciprocal homicide described in the literature. Other manners of death are discussed, including homicide by a third party, homicide-suicide, and suicide pact.